No Coincidence?

This paper critically examines coincidence arguments and evolutionary debunking arguments against non-naturalist realism in metaethics. It advances a version of these arguments that goes roughly like this: Given a non-naturalist, realist metaethic, it would be cosmically coincidental if our first order normative beliefs were true. This coincidence undermines any prima facie justification enjoyed by those beliefs

Monoklonale Antikörper zur Modulation der humanen T-Zellreaktivität gegen porzines Xenoantigen

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Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response

Rhinovirus (RV) infection is a major cause of asthma exacerbations which may be due to a deficient innate immune response in the bronchial epithelium. We hypothesized that the pleiotropic cytokine, TGF-?, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-?(2) increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-? antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-?(2) levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-? on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-? and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-? contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3

Targeted therapy in renal cell carcinoma: moving from molecular agents to specific immunotherapy

Non-specific immunotherapy has been for a long time a standard treatment option for patients with metastatic renal cell carcinoma but was redeemed by specific targeted molecular therapies, namely the VEGF and mTOR inhibitors. After moving treatment for mRCC to specific molecular agents with a well-defined mode of action, immunotherapy still needs this further development to increase its accuracy. Nowadays, an evolution from a rather non-specific cytokine treatment to sophisticated targeted approaches in specific immunotherapy led to a re-launch of immunotherapy in clinical studies. Recent steps in the development of immunotherapy strategies are discussed in this review with a special focus on peptide vaccination which aims at a tumor targeting by specific T lymphocytes. In addition, different combinatory strategies with immunomodulating agents like cyclophosphamide or sunitinib are outlined, and the effects of immune checkpoint modulators as anti-CTLA-4 or PD-1 antibodies are discussed

ENGINE PERFORMANCE ON ATOMIZATION OF FUEL INJECTOR: A REVIEW

The impact of the fuel injection of fuel atoms on engine performance has been investigated to improve fuel efficiency and waste disposal features. The fuel swirl method for injection atomization was evaluated both by the analysis of the fuel flow and the sample test. The goal of the paper is to establish good fuel atomization over the range of engine performance. As a result of our studies, it has been concluded that the desired atomization can be achieved when gasoline is thrown into a circular motion. Fuel spray and atomization features play an important role in the performance of internal combustion engines. An atomization study to evaluate the numerical fuel injection used in the IGC (Inner Guide-vane Combustor) under various combination and performance conditions has been performed to determine the suspension of the proposed fuel injection to be used in the IGC. Additional results have shown that a single-hole fuel injection, forward injection direction, and a splash of

Hypertonicity-affected genes are differentially expressed in clear cell renal cell carcinoma and correlate with cancer-specific survival

The heterogeneity of renal cell carcinoma (RCC) subtypes reflects the cell type of origin in the nephron, with consequences for therapy and prognosis. The transcriptional cues that determine segment-specific gene expression patterns are poorly understood. We recently showed that hypertonicity in the renal medulla regulates nephron-specific gene expression. Here, we analyzed a set of 223 genes, which were identified in the present study by RNA-Seq to be differentially expressed by hypertonicity, for the prediction of cancer-specific survival (CSS). Cluster analyses of these genes showed discrimination between tumor and non-tumor samples of clear cell RCC (ccRCC). Refinement of this gene signature to a four-gene score (OSM score) through statistical analyses enabled prediction of CSS in ccRCC patients of The Cancer Genome Atlas (TCGA) (n = 436) in univariate (HR = 4.1; 95% CI: 2.78-6.07; p = 4.39 × 10(-13)), and multivariate analyses including primary tumor (T); regional lymph node (N); distant metastasis (M); grading (G)(p = 2.3 × 10(-5)). The OSM score could be validated in an independent ccRCC study (n = 52) in univariate (HR = 1.29; 95% CI = 1.05-1.59; p = 0.011) and multivariate analyses (p = 0.016). Cell culture experiments using RCC cell lines demonstrated that the expression of the tumor suppressor ELF5 could be restored by hypertonicity. The innovation of our novel gene signature is that these genes are physiologically regulated only by hypertonicity, thereby providing the possibility to be targeted for therapy

Clarifying ethical intuitionism

In recent years there has been a resurgence of interest in Ethical Intuitionism, whose core claim is that normal ethical agents can and do have non-inferentially justified first-order ethical beliefs. Although this is the standard formulation, there are two senses in which it is importantly incomplete. Firstly, ethical intuitionism claims that there are non-inferentially justified ethical beliefs, but there is a worrying lack of consensus in the ethical literature as to what non-inferentially justified belief is. Secondly, it has been overlooked that there are plausibly different types of non-inferential justification, and that accounting for the existence of a specific sort of non-inferential justification is crucial for any adequate ethical intuitionist epistemology. In this context, it is the purpose of this paper to provide an account of non- inferentially justified belief which is superior to extant accounts, and, to give a refined statement of the core claim of ethical intuitionism which focuses on the type of non- inferential justification vital for a plausible intuitionist epistemology. Finally, it will be shown that the clarifications made in this paper make it far from obvious that two intuitionist accounts, which have received much recent attention, make good on intuitionism’s core claim